Bone Marrow Transplant Success Depends on the Dose

Scientists from the University of Southern California say they have found clues about how the dose of transplanted bone marrow might affect patients undergoing this risky procedure, frequently used to treat cancer and blood diseases. Specifically, Casey Brewer, Ph.D., and colleagues in the laboratory of Rong Lu, Ph.D., discovered that transplantation dose affects the behavior of the blood-forming stem cells in bone marrow hematopoietic stem cells (HSCs).

To track these cells' behavior, the researchers whose study (“Transplantation Dose Alters the Differentiation Program of Hematopoietic Stem Cells”) appears in Cell Reports, barcoded individual mouse HSCs with a genetic marker and observed their contributions to forming blood. Every HSC is capable of acting as a generalist, producing all of the specialized types of blood cells following bone marrow transplantation. However, the investigators observed that only 20–30% of HSCs took on this generalist role, contributing all of the most abundant types of white blood cells (granulocytes, B cells, and T cells). This relatively small group of generalist HSCs produced a disproportionately large amount of blood.

The remaining 70–80% of HSCs were more strategic. When facing a scarcity of transplanted bone marrow at the lowest dose, these HSCs prioritized T-cell production. At higher transplantation doses, these HSCs opted to differentiate early, producing a balanced array of T cells and B cells.

“The dose of transplanted bone marrow has strong and lasting effects on how HSCs specialize and coordinate their behavior,” noted Dr. Lu, senior author and assistant professor of stem cell biology and regenerative medicine. “This suggests that altering transplantation dose could be a tool for improving outcomes for patients, i.e., promoting bone marrow engraftment, reducing the risk of infection, and ultimately saving lives.”